GDF10 and IDO1 as a thyroid cancer prognostic biomarker associated with immune infiltration.

Objection: The aim of this work is to screen the immune-related genes to predict the prognosis and provide a new direction of treatment for patients with thyroid cancer (THCA). Methods: The mRNA and clinical features of THCA patients were collected from the Cancer Genome Atlas (TCGA) databases. The immune-related genes were obtained from the ImmPort databases. The bio-information methods were performed to screen the differential expression genes (DEGs) and genes related to immunity between the THCA patients and normal individuals. On this basis, the hub prognosis immunity genes were screened by Veen. The related genes were obtained by constructing the protein-protein interaction network. The enrichment analyses were performed based on the protein and protein interaction (PPI) related genes. The hub immune checkpoint was screened by correlation analysis. Finally, the hub gene and the immunity checkpoint-miRNA (or transcription factor, drug) interaction network were constructed. A drug-sensitive analysis also was performed. Results: The GDF10 was screened. The PPI genes were enriched in the TGF-beta signaling pathway, signaling pathways regulating, the pluripotency of stem cells, Cytokine-cytokine receptor interaction, and so on. The hub immunity checkpoint IDO1 was obtained. The joint indicator of two hub genes was positively related to the thyroid differentiation score. Three interaction factors were found to be related to the two hub genes, and 7 kinds of drugs screened act on the two hub genes at the same time. Conclusion: This work indicated that immune-related gene GDF10 and immune checkpoint IDO1 are important for the prognosis prediction of THCA patients, and immunity is involved in the proliferation, and differentiation of tumor cells.

Squamous cell carcinoma of the cystic duct: A case report and literature review.

RATIONALE: Pure squamous cell carcinoma (SCC) of the gallbladder is a rare malignant biliary tract tumor predominantly found in the body and neck of the gallbladder. However, its occurrence in the cystic duct is even rarer. Given its rarity, no established guidelines or consensus currently exist regarding the treatment of pure SCC of the gallbladder. We report an unusual case of SCC originating from the cystic duct with the intent of providing insights into the therapeutic approach for this type of malignancy. PATIENT CONCERNS: A male patient presented to our hospital with acute cholecystitis. Unexpectedly, imaging revealed gallbladder malignancy. DIAGNOSES: Pathologic examination after surgery confirmed SCC of the cystic duct. INTERVENTIONS: Despite elevated bilirubin levels, we were able to exclude hilar involvement, enabling radical tumor resection. Intraoperatively, we discovered that the tumor was located in the cystic duct, a site associated with a high likelihood of invasion into neighboring organs. The tumor demonstrated a predominantly exophytic growth pattern, which prompted us to refrain from extending the resection range, thereby striking a balance between complete tumor removal and surgical trauma. We performed liver wedge resection only to ensure a negative resection margin while preserving the anatomical structure to the greatest extent possible. Postoperative recovery was rapid and uncomplicated. Pathological examination confirmed pure SCC, which led us to initiate a regimen of nab-paclitaxel and cisplatin, which is known to be effective in other organ SCCs. Remarkably, the patient experienced a rare and severe posttreatment cardiovascular event. Consequently, we switched the patient to a chemotherapy regimen of gemcitabine and cisplatin, which ultimately yielded positive clinical outcomes. OUTCOMES: no evidence of tumor recurrence was observed within 1 year after surgery. LESSONS: The diagnosis and therapeutic strategy for rare tumors such as gallbladder SCC should be meticulously tailored based on their unique characteristics to optimize postoperative patient outcomes.

An investigation of the microstructure and mechanical properties of dental zirconia manufactured by digital light processing 3D printing.

OBJECTIVES: This study was performed to investigate the microstructure and mechanical properties of dental zirconia manufactured by digital light processing (DLP) 3D printing and the clinical application prospects of this material. METHODS: The experiment (DLP) group was zirconia manufactured by DLP 3D printing, and the control (MILL) group was milled zirconia. The density, grain size, and phase composition were measured to study the microstructure. Flexural strength was measured by using three-point bending tests, while Vickers hardness was determined through a Vickers hardness tester. Fracture toughness was tested using the single-edge V-notched beam method. RESULTS: Zirconia density of the DLP group was (6.019 8±0.021 3) g·cm-3, and the average grain size was (0.603 0±0.032 6) µm, but without statistical difference with the corresponding values of the MILL group (P>0.05). Tetragonal phase was found in the X-ray diffraction patterns of the DLP and MILL groups. The flexural strength of the DLP group was (1 012.7±125.5) MPa, and Vickers hardness was (1 238.5±10.8) HV1, which was slightly lower than that of the MILL group (P<0.05). The fracture toughness of the DLP group was (7.22±0.81) MPa·m1/2, which was not statistically different from that of the MILL group (P>0.05). CONCLUSIONS: Zirconia manufactured by DLP 3D printing had microstructure and mechanical properties similar to those of the milled zirconia. Only the flexural strength and the Vickers hardness of the experimental zirconia were slightly lower than those of the milled zirconia. Therefore, DLP-manufactured zirconia has a promising future for clinical use.

Successful totally laparoscopic right trihepatectomy following conversion therapy for hepatocellular carcinoma: A case report.

BACKGROUND: About 20%-30% of newly diagnosed hepatocellular carcinoma (HCC) patients are surgically feasible due to a variety of reasons. Active conversion therapy may provide opportunities of surgery for these patients. Nevertheless, the choice of surgical procedure is controversial after successful conversion therapy. We report a patient with HCC who underwent successful laparoscopic right trisectionectomy after conversion therapy with portal vein embolization and transarterial chemoembolization. CASE SUMMARY: A 67-year-old male patient presented to our hospital with epigastric distention/ discomfort and nausea/vomiting for more than 1 mo. Contrast-enhanced computed tomography scan of the abdomen demonstrated multiple tumors (the largest was ≥ 10 cm in diameter) located in the right liver and left medial lobe, and the left lateral lobe was normal. The future remnant liver (FRL) of the left lateral lobe accounted for only 18% of total liver volume after virtual resection on the three-dimensional liver model. Conversion therapy was adopted after orally administered entecavir for antiviral treatment. First, the right portal vein was embolized. Then tumor embolization was performed via the variant hepatic arteries. After 3 wk, the FRL of the left lateral lobe accounted for nearly 30% of the total liver volume. Totally laparoscopic right trisectionectomy was performed under combined epidural and general anesthesia. The in situ resection was performed via an anterior approach. The operating time was 240 min. No clamping was required during the surgery, and the intraoperative blood loss was 300 mL. There were no postoperative complications such as bile leakage, and the incision healed well. The patient was discharged on the 8th postoperative day. During the 3-mo follow-up, there was no recurrence and obvious hyperplasia of residual liver was observed. Alpha-fetoprotein decreased significantly and tended to be normal. CONCLUSION: Due to the different biological characteristics of the liver cancer and the pathophysiological features of the liver from other organs, the conversion treatment should take into account both the feasibility of tumor downstaging and the volume and function of the remnant liver. Our case provides a reference for clinicians in terms of both conversion therapy and laparoscopic right trisectionectomy.

Liver dual arterial blood supply maintains liver regeneration: Analysis of signaling pathways in rats.

Liver dual arterial blood supply (LDABS) could increase blood supply to the liver and maintain normal liver regeneration in patients with compromised portal vein. The current study attempted to examine the underlying molecular mechanisms. Male Sprague­Dawley rats randomly received partial hepatectomy (PH) alone or PH followed by LDABS. Liver regeneration was assessed by histological examination, liver function and liver regeneration rate (LRR). Whole­genome oligo microarray analysis was used to compare gene expression profile between rats receiving PH and rats receiving PH plus LDABS. Key genes identification was validated using a MAPK signaling polymerase chain reaction (PCR) array. The extent of liver regeneration in rats receiving PH plus LDABS was comparable to that in rats receiving PH alone. The differentially expressed genes were enriched in 12 signaling pathways in two groups. MAPK signaling pathway, NF­kappa B signaling pathway, and Toll­like receptor signaling pathway were involved in LDABS­mediated liver regeneration, with Retinoblastoma 1 (Rb1), Cyclin D1, Cyclin­dependent kinase 4, Mitogen­activated protein kinase 10 (Mapk10) and CAMP responsive element binding protein 1 genes in the initiation phase, Kirsten rat sarcoma viral oncogene homolog (Kras), tumor protein 53, MYC proto­oncogene, BHLH transcription factor, Cyclin E1 and Heat shock protein family B (small) member 1 genes in the proliferation phase, Kras, Rb1, Jun proto­oncogene, AP­1 transcription factor subunit, Cyclin D2 and Mapk10 genes in the termination phase were identified as key genes in LDABS­mediated liver regeneration using MAPK signaling PCR array analysis.

Genetic polymorphisms of interleukin-16 and risk of knee osteoarthritis.

BACKGROUND: Interleukin-16 (IL-16), a pleiotropic cytokine, plays a fundamental role in inflammatory diseases. This study investigates the association between IL-16 polymorphisms and the risk of knee osteoarthritis (OA) in a Chinese population. METHODS: The IL-16 rs11556218, rs4072111, and rs4778889 polymorphisms were determined in 150 knee OA cases and 147 healthy controls through polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The results suggested that the variants in IL-16 gene rs11556218 site were associated with a decreased knee OA risk after adjusting for age, sex, BMI, and smoking and drinking status (TG vs. TT: OR, 0.69; 95% CI, 0.53-0.89; P = 0.006; GG vs. TT: OR, 0.64; 95% CI, 0.45-0.90; P = 0.042; dominant model: OR, 0.68; 95% CI, 0.29-0.87; P = 0.002; G vs. T allele: OR, 0.77; 95% CI, 0.66-0.90; P = 0.003). Similarly, subjects bearing the rs4072111 variant genotypes and alleles also had a lower susceptibility to knee OA compared with those bearing the wild-type (CT vs. CC: OR, 0.66; 95% CI, 0.53-0.83; P = 0.002; TT vs. CC: OR, 0.57; 95% CI, 0.40-0.82; P = 0.027; dominant model: OR, 0.65; 95%, CI 0.52-0.80; P <0.001; T vs. C allele: OR, 0.69; 95% CI, 0.58-0.81; P <0.001). Further, the C allele and the combined genotype (CC+CT) of rs4778889 were associated with a slightly decreased risk of knee OA. In addition, we found two high-risk haplotypes: TTT (OR, 3.70) and GCC (OR, 6.22). Finally, serum IL-16 levels of knee OA patients were significantly higher than those of controls (P = 0.001). CONCLUSIONS: Despite the small sample size, this is the first study suggesting IL-16 gene polymorphisms to be associated with the risk of knee OA.

Osteopontin knockdown suppresses the growth and angiogenesis of colon cancer cells.

AIM: To investigate the effects of osteopontin (OPN) gene expression knockdown on colon cancer Lovo cells in vitro. METHODS: Four candidate small interfering RNA (siRNA) constructs targeting the OPN gene and a scrambled control sequence (NC-siRNA) were synthesized and inserted into a pGPU6/GFP/Neo expression vector. After confirmation by restriction enzyme digestion and DNA sequencing, the recombinant plasmids were subsequently transfected into a human colon cancer cell line (Lovo) using a liposome transfection method. Stably transfected cells were maintained with G418 selection and referred to as Lovo-OPN-1, -2, -3, -4, and Lovo-NC cells. Knockdown efficiency of each of the four siRNA constructs was determined by real-time reverse transcription polymerase chain reaction assays and western blotting, and the construct with the most effective silencing was used for subsequent experiments. Cell proliferation, adhesion, and Matrigel invasion assays were performed to analyze the effects of OPN knockdown in stably transfected Lovo cells. The levels of four angiogenic factors, namely vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, MMP-9 and urokinase plasminogen activator were detected by enzyme-linked immunosorbent assays (ELISA). RESULTS: Recombinant vectors containing OPN-specific and scrambled siRNA sequences were successfully constructed and stably transfected into Lovo cells. Compared with the control Lovo and Lovo-NC cells, the levels of OPN mRNA and protein expression in Lovo-OPN-1, -2, -3, and -4 were significantly reduced (all P < 0.05), with the most efficient reduction observed in Lovo-OPN-4 cells (P < 0.05). Relative to untransfected Lovo cells, OPN mRNA expression levels in Lovo-NC and Lovo-OPN-4 cells were 1.008 ± 0.067 and 0.160 ± 0.023, respectively. The relative OPN protein expression levels in Lovo, Lovo-NC, and Lovo-OPN-4 cells were 3.024 ± 0.211, 2.974 ± 0.630, and 0.121 ± 0.008, respectively. Moreover, transfection with the scrambled sequence had no effect on the expression of OPN. After 24, 48, 72, and 96 h of cultivation, absorption values at 450 nm to assess proliferation of Lovo-OPN-4 cells were 0.210 ± 0.017, 0.247 ± 0.024, 0.314 ± 0.037, and 0.359 ± 0.043, respectively, which were significantly lower than those of Lovo (0.244 ± 0.031, 0.313 ± 0.024, 0.513 ± 0.048 and 0.783 ± 0.051) and Lovo-NC cells (0.241 ± 0.029, 0.309 ± 0.022, 0.563 ± 0.023, and 0.735 ± 0.067) (all P < 0.05). The absorption values at 595 nm, which were measured in a cell adhesion assay, showed that adhesion of Lovo-OPN-4 cells (0.215 ± 0.036) was significantly decreased compared to Lovo (0.490 ± 0.037) and Lovo-NC cells (0.462 ± 0.043) (P < 0.05). The number of invasive Lovo-OPN-4 cells (16.1 ± 1.9) was also significantly decreased compared to Lovo (49.9 ± 5.4) and Lovo-NC cells (48.8 ± 4.5) (P < 0.05). ELISA assays showed significant reductions in Lovo-OPN-4 cells compared to Lovo and Lovo-NC cells with regard to the expression of VEGF (1687.85 ± 167.84 ng/L vs 2348.54 ± 143.80 ng/L and 2284.39 ± 138.62 ng/L, respectively), MMP-2 (2966.07 ± 177.36 µg/L vs 4084.74 ± 349.54 µg/L and 4011.41 ± 424.48 µg/L, respectively), MMP-9 (3782.89 ± 300.64 µg/L vs 5062.90 ± 303.02 µg/L and 4986.38 ± 300.75 µg/L, respectively) and uPA (1152.69 ± 120.79 µg/L vs 1380.90 ± 147.25 µg/L and 1449.80 ± 189.92 µg/L, respectively) (all P < 0.05). CONCLUSION: Knockdown of OPN gene expression suppresses colon cancer cell growth, adherence, invasion, and expression of angiogenic factors.

Development of a new auxiliary heterotopic partial liver transplantation technique using a liver cirrhosis model in minipigs: Preliminary report of eight transplants.

This study aimed to develop a new auxiliary heterotopic partial liver transplantation (AHPLT) technique in minipigs using a model of liver cirrhosis. Based on our previous study, 14 minipigs were induced to cirrhosis by administration of carbon tetrachloride (CCl(4)) through intraperitoneal injection. All of the cirrhotic animals were utilized as recipients. The donor's liver was placed on the recipient's splenic bed, and the anastomosis was performed as follows: end-to-end anastomosis between the donor's portal vein and the recipient's splenic vein, end-to-side anastomosis between the donor's suprahepatic vena cava and the recipient's suprahepatic vena cava, and end-to-end anastomosis between the donor's hepatic artery and the recipient's splenic artery. The common bile duct of the donor was intubated and bile was collected with an extracorporeal bag. Vital signs, portal vein pressure (PVP), hepatic venous pressure (HVP) and portal vein pressure gradient (PVPG) were monitored throughout the transplantation. All 8 minipigs that developed liver cirrhosis were utilized to establish the new AHPLT; 7 cases survived. Following the surgical intervention, the PVP and PVPG of the recipients were lower than those prior to the operation (P<0.05), whereas the PVP and PVPG of the donors increased significantly compared to those of the normal animals (P<0.05). A new operative technique for AHPLT has been successfully described herein using a model of liver cirrhosis.

Right hepatic arterial pseudoaneurysm with hemobilia following minilaparotomy cholecystectomy: a rare complication.

Hepatic arterial pseudoaneurysm with hemobilia occurs less frequently as a complication of minilaparotomy cholecystectomy than laparoscopic cholecystectomy; however, given its severe nature, it needs to be managed promptly. This report presents a case of right hepatic artery pseudoaneurysm with hemobilia in a 36-year-old woman who underwent minilaparotomy cholecystectomy 5 weeks earlier. Angiography with embolization was carried out as definitive treatment.

Protective effect of pyrroloquinoline quinone against Abeta-induced neurotoxicity in human neuroblastoma SH-SY5Y cells.

The neurotoxicity of aggregated beta-amyloid (Abeta) has been implicated as a critical cause in the pathogenesis of Alzheimer's disease (AD). It can cause neurotoxicity in AD by evoking a cascade of oxidative damage-dependent apoptosis to neurons. In the present study, we for the first time investigated the protective effect of pyrroloquinoline quinone (PQQ), an anionic, water soluble compound that acts as a redox cofactor of bacterial dehydrogenases, on Abeta-induced SH-SY5Y cytotoxicity. Abeta(25-35) significantly reduced cell viability, increased the number of apoptotic-like cells, and increased ROS production. All of these phenotypes induced by Abeta(25-35) were markedly reversed by PQQ. PQQ pretreatment recovered cells from Abeta(25-35)-induced cell death, prevented Abeta(25-35)-induced apoptosis, and decreased ROS production. PQQ strikingly decreased Bax/Bcl-2 ratio, and suppressed the cleavage of caspase-3. These results indicated that PQQ could protect SH-SY5Y cells against beta-amyloid induced neurotoxicity.

[Expression of CK20 mRNA in the peripheral blood around postoperative chemotherapy in patients with gastric cancer and its clinical significance].

OBJECTIVE: To investigate whether CK20 mRNA expression level could be considered as an effective molecular indicator for evaluation of chemotherapy sensitivity. METHODS: All samples of peripheral blood were taken from 31 gastric cancer patients undergone radical operation a week before postoperative chemotherapy, at the first day of chemotherapy point, and after the first cycle of chemotherapy respectively, and subjected to FQ RT-PCR assay for CK20 mRNA. The chemotherapy scheme was FOLFOX 4. The control group was 15 healthy volunteers. RESULTS: Aomng the 31 gastric cancer patients, the value of CK20 mRNA before postoperative chemotherapy was increased (2.96+/-2.27 vs 2.22+/-2.12, t=2.10, P<0.05) in 25 positive cases, and then declined after chemotherapy(2.05+/-1.86 vs 2.96+/-2.27, t=2.50, P<0.05) in 24 positive cases. The expression level of CK20 mRNA in patients before chemotherapy was increased in 16 cases(51.6%), declined in 9 cases(29.0%) and stabilized as negative in 6 cases(19.4%). After chemotherapy the level of CK20 mRNA was increased in 7 cases(22.6%), declined in 17 cases (54.8%) and stabilized as negative in 7 cases(22.6%), there was significant difference between the two groups(chi(2)=6.06, P<0.05). CONCLUSIONS: The expression level of CK20 mRNA in the peripheral blood detected by FQ RT-PCR in patients with gastric cancer declines after postoperative adjuvant chemotherapy. Different individuals have different sensitivity to chemotherapeutics. Dynamic monitoring CK20 mRNA should be considered as an effective index to evaluate the efficacy of postoperative adjuvant chemotherapy.